Abstract |
Assembly of C5b-9 on cell membranes results in transmembrane channels and causes cell death. When the number of C5b-9 molecules is limited, nucleated cells are able to escape cell death by endocytosis and by shedding of membranes bearing C5b-9. Sublytic CSb-9 induces proto-oncogenes, activates the cell cycle, and enhances cell survival. In addition, C5b-9 reverses the differentiated phenotype of postmitotic cells, such as oligodendrocytes and skeletal muscle cells. The signal transduction pathways responsible for cell cycle activation by CSb-9 include Gi-mediated activation of extracellular signal-regulated kinase 1 and phosphatidylinositol 3-kinase (PI3-K). Cell survival enhanced by C5b-9 is mediated by the PI3-K/Akt pathway, which inhibits apoptosis through regulation of BAD. These findings indicate that complement activation and membrane assembly of sublytic C5b-9 play an important role in inflammation by promoting cell proliferation and by rescuing apoptotic cells.
|
Authors | H G Rus, F I Niculescu, M L Shin |
Journal | Immunological reviews
(Immunol Rev)
Vol. 180
Pg. 49-55
(Apr 2001)
ISSN: 0105-2896 [Print] England |
PMID | 11414362
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
|
Chemical References |
- BAD protein, human
- BCL2L1 protein, human
- Carrier Proteins
- Complement Membrane Attack Complex
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-bcl-2
- Retinoblastoma Protein
- bcl-2-Associated X Protein
- bcl-Associated Death Protein
- bcl-X Protein
- AKT1 protein, human
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
|
Topics |
- Animals
- Apoptosis
(physiology)
- Carrier Proteins
(physiology)
- Cell Cycle
(physiology)
- Cell Differentiation
(physiology)
- Cell Membrane Permeability
- Complement Membrane Attack Complex
(physiology)
- Endocytosis
- Gene Expression Regulation
(physiology)
- Humans
- MAP Kinase Signaling System
(physiology)
- Mitochondria
(physiology)
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
(physiology)
- Necrosis
- Phosphatidylinositol 3-Kinases
(physiology)
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins
(physiology)
- Proto-Oncogene Proteins c-akt
- Proto-Oncogene Proteins c-bcl-2
(physiology)
- Proto-Oncogenes
- Retinoblastoma Protein
(physiology)
- bcl-2-Associated X Protein
- bcl-Associated Death Protein
- bcl-X Protein
|